Multi-well plates, or two-dimensionally bound arrays of wells or reaction chambers, are commonly employed in research and clinical procedures for the screening and evaluation of multiple samples. Multi-well plates are especially useful in conjunction with automated thermal cyclers for performing the widely used polymerase chain reaction, or "PCR," and for DNA cycle sequencing and the like. They are also highly useful for biological micro-culturing and assay procedures, and for performing chemical syntheses on a micro scale.
Multi-well plates may have wells or tubes that have single openings at their top ends, similar to conventional test tubes and centrifuge tubes, or they may incorporate second openings at their bottom ends which are fitted with frits or filter media to provide a filtration capability. As implied above, multi-well plates are most often used for relatively small scale laboratory procedures and are therefore also commonly known as "microplates."
Multi-well plates are typically comprised of a plurality of plastic tubes arranged in rectangular planar arrays of either 6.times.8 (a 48-well plate) or 8.times.12 (a 96-well plate) tubes with an industry standard 9 mm (0.35 in.) center-to-center tube spacing (or fractions thereof). A horizontally disposed tray or plate portion generally extends integrally between each tube, interconnecting each tube with its neighbor in cross-web fashion, although in certain square-shaped tube designs the tubes may share the walls of their neighbors along the height of the tubes. In the case of multi-well plates that are of the non-filtration variety, the bottoms of the tubes may be of a rounded conical shape (as generally used for thermal cycling and to ensure complete transfer of samples), or they may be flat-bottomed (typical with either round or square-shaped designs used with optical readers). Multi-well "plates" may also exist in a "strip" form wherein but a single planar row of interconnected tubes is provided.
It will be apparent that as many as 96 individual reaction mixtures might be simultaneously subjected to, for example, PCR treatment by placing a single multi-well plate within a thermal cycler unit. Most commercial thermal cyclers that are presently available have heating/cooling blocks with conically shaped depressions, typically 96 in number, which are specifically designed and arrayed for mateably receiving the lower portion of the tubes of multi-well plates so that intimate and uniform heating of the PCR reaction mixtures contained within the wells (tubes) may occur.
It is becoming increasingly the case with a variety of operations, however, and especially with PCR, that it would be extremely beneficial to treat or manipulate, at the same time, a multitude of individual samples much greater than 96 in number. This is the case in the human genome project, for example. When a large number of samples must be processed, it is necessary to use a number of multi-well plates, which then must be handled sequentially one at a time. A number of multi-well plates may also be required for storing large numbers of samples.
In the past couple of years, multi-well plates in a 384 tube, 16.times.24 array format, have appeared on the laboratory scene in an attempt to offer to the researcher or clinician the ability to multiplicatively increase the processing capability for the assay or reaction process that is being carried out. These new 384-well plates have the same general dimensions or "footprint" as the standard 96-well plates, but have four wells occupying the same space as a single well (and associated cross-webbing) in a 96-well plate.
The 384-well plates which are currently available may be of a design similar to standard 96-well plates, wherein discrete tubes are present but in which the tubes have smaller diameter tube openings (and a correspondingly smaller center-to-center tube spacing as well). They may also be in a form such as the 384-well plate design currently offered by Nunc, Inc. of Naperville, Ill., wherein square "tubes" are provided with each "tube" sharing the walls of its neighbors in contiguous fashion.
The new 384-well plates do offer advantages in that sample density is quadrupled, and these plates, having the same footprint as the 96-well plates, are compatible with a number of existing devices, including heating blocks for incubation purposes, microplate readers, and various robotic systems. The 384-well plates also optimize bench top and storage space, especially with regard to the extended storage of samples in refrigerator and freezer space, such space generally being in limited supply in most laboratories and clinics.
There is at least one area in particular, however, where the 384-well plates as are presently known are severely deficient, and that is with regard to PCR thermal cycling. Currently available 384-well plates are not compatible with the depression design found in existing (96 format) PCR heating blocks. As noted above, PCR heating blocks are specifically designed to hold and heat tubes that are arrayed 96 in number. Thus, with regard to PCR testing, it is still necessary to employ more than one 96-well plate in sequential fashion for evaluation of more than 96 samples. Only very recently has any manufacturer marketed a 384-well thermal cycler. As it presently stands, if a laboratory or clinic wishes to have available the option to simultaneously treat more than 96 samples, it must purchase the new 384-well design thermal cycler or a new 384 depression heating block for an existing unit or, of course, purchase more than one 96-well thermal cycler. All of these options are expensive and, in the latter case, additional precious laboratory space is consumed by yet another instrument.
Because of the limitations associated with presently available multi-well plates which offer more than 96 wells, a great need still exists for a multi-well plate that is capable of providing a multiplicatively increased number of sample wells greater than 96, but which retains a standard 96-well plate footprint and yet is also suitable for use in conjunction with the 96-depression heating blocks of existing thermal cyclers.